TY - JOUR A1 - Li, Minghao A1 - Pamporaki, Christina A1 - Fliedner, Stephanie M. J. A1 - Timmers, Henri J. L. M. A1 - Nölting, Svenja A1 - Beuschlein, Felix A1 - Prejbisz, Aleksander A1 - Remde, Hanna A1 - Robledo, Mercedes A1 - Bornstein, Stefan R. A1 - Lenders, Jacques W. M. A1 - Eisenhofer, Graeme A1 - Bechmann, Nicole T1 - Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion JF - Discover Oncology N2 - Background The presence or future development of metastatic pheochromocytomas or paragangliomas (mPPGLs) can be difficult to diagnose or predict at initial presentation. Since production of catecholamines from mPPGLs is different from non-metastatic tumors (non-mPPGLs), this study aimed to clarify whether presenting catecholamine-related signs and symptoms (cSS) might also differ. Methods The study included 249 patients, 43 with mPPGL and 206 with non-mPPGL. Clinical data at the time of biochemical diagnosis (i.e. at entry into the study) were used to generate a cumulative score of cSS for each patient. Results Patients with mPPGL were significantly younger (43.3 ± 14 vs. 48.9 ± 16.1 years) and included a lower proportion of females (39.5% vs. 60.7%) than patients with non-mPPGLs. Frequencies of signs and symptoms did not differ between the two groups. Patients with mPPGLs had lower (P < 0.001) urinary excretion of epinephrine (3.5 (IQR, 1.9—6.5) µg/day) than those with non-mPPGLs (19.1 (IQR, 4.3—70.2) µg/day). There was no difference in urinary excretion of norepinephrine. In patients with mPPGLs a high cSS score was associated with high urinary excretion of norepinephrine and normetanephrine. In contrast, in patients with non-mPPGLs, a high cSS was associated with high urinary excretion of epinephrine and metanephrine. Conclusion Although presenting signs and symptoms were associated with production of norepinephrine in patients with mPPGLs and of epinephrine in patients with non-mPPGLs, there were no differences in signs and symptoms between the two groups. Therefore, consideration of signs and symptoms does not appear helpful for distinguishing patients with and without mPPGLs. KW - pheochromocytoma KW - paraganglioma KW - metastatic KW - signs KW - symptoms KW - catecholamines Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-309901 SN - 2730-6011 VL - 12 ER - TY - JOUR A1 - Minner, S. A1 - Schreiner, J. A1 - Saeger, W. T1 - Adrenal cancer: relevance of different grading systems and subtypes JF - Clinical and Translational Oncology N2 - Purpose The subclassification of adrenal cancers according to the WHO classification in ordinary, myxoid, oncocytic, and sarcomatoid as well as pediatric types is well established, but the criteria for each subtype are not sufficiently determined and the relative frequency of the different types of adrenal cancers has not been studied in large cohorts. Therefore, our large collection of surgically removed adrenal cancers should be reviewed o establish the criteria for the subtypes and to find out the frequency of the various types. Methods In our series of 521 adrenal cancers the scoring systems of Weiss et al., Hough et al., van Slooten et al. and the new Helsinki score system were used for the ordinary type of cancer (97% of our series) and the myxoid type (0.8%). For oncocytic carcinomas (2%), the scoring system of Bisceglia et al. was applied. Results Discrepancies between benign and malignant diagnoses from the first thee classical scoring systems are not rare (22% in our series) and could be resolved by the Helsinki score especially by Ki-67 index (more than 8% unequivocally malignant). Since all our cancer cases are positive in the Helsinki score, this system can replace the three elder systems. For identification of sarcomatoid cancer as rarest type in our series (0.2%), the scoring systems are not practical but additional immunostainings used for soft tissue tumors and in special cases molecular pathology are necessary to differentiate these cancers from adrenal sarcomas. According to the relative frequencies of the different subtypes of adrenal cancers the main type is the far most frequent (97%) followed by the oncocytic type (2%), the myxoid type (0.8%) and the very rare sarcomatoid type (0.2%). Conclusions The Helsinki score is the best for differentiating adrenal carcinomas of the main, the oncocytic, and the myxoid type in routine work. Additional scoring systems for these carcinomas are generally not any longer necessary. Signs of proliferation (mitoses and Ki-67 index) and necroses are the most important criteria for diagnosis of malignancy. KW - adrenal KW - cancer KW - cancer types KW - classification Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308479 SN - 1699-048X SN - 1699-3055 VL - 23 IS - 7 ER - TY - JOUR A1 - Adolf, Christian A1 - Braun, Leah T. A1 - Fuss, Carmina T. A1 - Hahner, Stefanie A1 - Künzel, Heike A1 - Handgriff, Laura A1 - Sturm, Lisa A1 - Heinrich, Daniel A. A1 - Schneider, Holger A1 - Bidlingmaier, Martin A1 - Reincke, Martin T1 - Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism JF - Endocrine N2 - Context Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. Patients and methods We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. Study design Observational longitudinal cohort study. Setting Tertiary care hospital. Results Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. Conclusion This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy. KW - aldosterone KW - osteocalcin KW - osteoporosis KW - hyperparathyroidism KW - cortisol Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-315966 SN - 1355-008X SN - 1559-0100 VL - 69 IS - 3 ER - TY - JOUR A1 - Bliziotis, Nikolaos G. A1 - Kluijtmans, Leo A. J. A1 - Soto, Sebastian A1 - Tinnevelt, Gerjen H. A1 - Langton, Katharina A1 - Robledo, Mercedes A1 - Pamporaki, Christina A1 - Engelke, Udo F. H. A1 - Erlic, Zoran A1 - Engel, Jasper A1 - Deutschbein, Timo A1 - Nölting, Svenja A1 - Prejbisz, Aleksander A1 - Richter, Susan A1 - Prehn, Cornelia A1 - Adamski, Jerzy A1 - Januszewicz, Andrzej A1 - Reincke, Martin A1 - Fassnacht, Martin A1 - Eisenhofer, Graeme A1 - Beuschlein, Felix A1 - Kroiss, Matthias A1 - Wevers, Ron A. A1 - Jansen, Jeroen J. A1 - Deinum, Jaap A1 - Timmers, Henri J. L. M. T1 - Pre- versus post-operative untargeted plasma nuclear magnetic resonance spectroscopy metabolomics of pheochromocytoma and paraganglioma JF - Endocrine N2 - Purpose Pheochromocytomas and Paragangliomas (PPGL) result in chronic catecholamine excess and serious health complications. A recent study obtained a metabolic signature in plasma from PPGL patients; however, its targeted nature may have generated an incomplete picture and a broader approach could provide additional insights. We aimed to characterize the plasma metabolome of PPGL patients before and after surgery, using an untargeted approach, and to broaden the scope of the investigated metabolic impact of these tumors. Design A cohort of 36 PPGL patients was investigated. Blood plasma samples were collected before and after surgical tumor removal, in association with clinical and tumor characteristics. Methods Plasma samples were analyzed using untargeted nuclear magnetic resonance (NMR) spectroscopy metabolomics. The data were evaluated using a combination of uni- and multi-variate statistical methods. Results Before surgery, patients with a nonadrenergic tumor could be distinguished from those with an adrenergic tumor based on their metabolic profiles. Tyrosine levels were significantly higher in patients with high compared to those with low BMI. Comparing subgroups of pre-operative samples with their post-operative counterparts, we found a metabolic signature that included ketone bodies, glucose, organic acids, methanol, dimethyl sulfone and amino acids. Three signals with unclear identities were found to be affected. Conclusions Our study suggests that the pathways of glucose and ketone body homeostasis are affected in PPGL patients. BMI-related metabolite levels were also found to be altered, potentially linking muscle atrophy to PPGL. At baseline, patient metabolomes could be discriminated based on their catecholamine phenotype. KW - PPGL KW - metabolomics KW - NMR KW - paired KW - plasma KW - operation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-326574 VL - 75 IS - 1 ER - TY - JOUR A1 - Nowotny, Hanna A1 - Ahmed, S. Faisal A1 - Bensing, Sophie A1 - Beun, Johan G. A1 - Brösamle, Manuela A1 - Chifu, Irina A1 - Claahsen van der Grinten, Hedi A1 - Clemente, Maria A1 - Falhammar, Henrik A1 - Hahner, Stefanie A1 - Husebye, Eystein A1 - Kristensen, Jette A1 - Loli, Paola A1 - Lajic, Svetlana A1 - Reisch, Nicole T1 - Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis JF - Endocrine N2 - Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives. KW - adrenal insufficiency KW - congenital adrenal hyperplasia KW - adrenal crisis KW - glucocorticoid replacement KW - hydrocortisone KW - stress instructions Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308769 SN - 1355-008X SN - 1559-0100 VL - 71 IS - 3 ER - TY - JOUR A1 - Amereller, Felix A1 - Deutschbein, Timo A1 - Joshi, Mamta A1 - Schopohl, Jochen A1 - Schilbach, Katharina A1 - Detomas, Mario A1 - Duffy, Leo A1 - Carroll, Paul A1 - Papa, Sophie A1 - Störmann, Sylvère T1 - Differences between immunotherapy-induced and primary hypophysitis—a multicenter retrospective study JF - Pituitary N2 - Objective Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) Design Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH. Methods All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected. Results Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002). Conclusions Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH. KW - primary hypophysitis KW - immunotherapy-induced hypophysitis KW - checkpoint inhibitors KW - immune-related adverse events KW - pembrolizumab KW - ipilimumab KW - nivolumab Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308704 SN - 1386-341X SN - 1573-7403 VL - 25 IS - 1 ER - TY - JOUR A1 - Güder, Gülmisal A1 - Rein, Eva von A1 - Flohr, Thomas A1 - Weismann, Dirk A1 - Schmitt, Dominik A1 - Störk, Stefan A1 - Frantz, Stefan A1 - Kratzer, Vincent A1 - Kendi, Christian T1 - Motion detectors as additional monitoring devices in the intensive care unit — a proof-of-concept study JF - Applied Sciences N2 - Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Grünwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes (“lying dead-still, with no or very shallow breathing”). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7%) were rated correctly. Ratings were false negative (FN: “no movements detected, but recorded”) in 7 out of 180 motion scenes (3.9%). Ratings were false positive (FP: “movements detected, but not recorded”) in 37 out of 150 scenes (24.7%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p < 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96%) and acceptable specificity (75%). Accuracy might increase further if activities are recorded continuously under real-world conditions. KW - motion detector KW - noncontact monitoring KW - Internet of Things devices Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-362404 SN - 2076-3417 VL - 13 IS - 16 ER - TY - JOUR A1 - Michalski, Kerstin A1 - Schlötelburg, Wiebke A1 - Hartrampf, Philipp E. A1 - Kosmala, Aleksander A1 - Buck, Andreas K. A1 - Hahner, Stefanie A1 - Schirbel, Andreas T1 - Radiopharmaceuticals for treatment of adrenocortical carcinoma JF - Pharmaceuticals N2 - Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [\(^{123/131}\)I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted. KW - adrenocortical carcinoma KW - theranostics KW - endoradiotherapy KW - IMAZA Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355901 SN - 1424-8247 VL - 17 IS - 1 ER - TY - JOUR A1 - Kimpel, Otilia A1 - Altieri, Barbara A1 - Dischinger, Ulrich A1 - Fuss, Carmina Teresa A1 - Kurlbaum, Max A1 - Fassnacht, Martin T1 - Early detection of recurrence and progress using serum steroid profiling by LC–MS/MS in patients with adrenocortical carcinoma JF - Metabolites N2 - Serum liquid chromatography–tandem mass spectrometry (LC–MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce. Patients were included in this retrospective study if pre-therapeutic hormone values, regular tumour evaluation by imaging, steroid measurements by LC–MS/MS, and details on therapies were available. The utility of steroid profiles in detecting recurrence or disease progression was assessed, whereby “endocrine progress” was defined by an elevation of at least 3 of 13 analysed hormones. Cohort A included 47 patients after R0 resection, of whom 15 experienced recurrence and 32 did not. In cohort B, 52 patients with advanced disease (including 7 patients of cohort A with recurrence) could be evaluated on 74 visits when progressive disease was documented. In 20 of 89 cases with documented disease progression, “endocrine progress” was detectable prior to radiological progress. In these cases, recurrence/progression was detected at a median of 32 days earlier by steroid measurement than by imaging, with 11-deoxycortisol and testosterone being the most sensitive markers. Notably, these patients had significantly larger tumour burden. In conclusion, steroid profiling by LC–MS/MS is of value in detecting recurrent/progressive disease in ACC. KW - adrenal cancer KW - follow-up KW - steroid measurement KW - liquid chromatography–tandem mass spectrometry (LC–MS/MS) Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-355839 SN - 2218-1989 VL - 14 IS - 1 ER - TY - JOUR A1 - Steinhardt, Maximilian J. A1 - Cejka, Vladimir A1 - Chen, Mengmeng A1 - Bäuerlein, Sabrina A1 - Schäfer, Julia A1 - Adrah, Ali A1 - Ihne-Schubert, Sandra M. A1 - Papagianni, Aikaterini A1 - Kortüm, K. Martin A1 - Morbach, Caroline A1 - Störk, Stefan T1 - Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study JF - Journal of Clinical Medicine N2 - Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients. KW - heart failure KW - chronic kidney disease KW - amyloidosis KW - SGLT2 inhibitors Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-356024 SN - 2077-0383 VL - 13 IS - 1 ER -